Optical biosensor matrix

ABSTRACT

A detection cell which is used as a component of an optical biosensor comprises a transparent base plate and a sample plate on the base plate. The sample plate has a matrix of wells extending through it to each to receive a sample. The base plate includes a waveguiding film and a diffraction grating means to in couple an incident light field into the waveguiding film beneath a well to generate a diffracted light field to enable detection of a change in the effective refractive index of the waveguiding film.

This application is a continuation of application Ser. No. 08/397,281,filed Apr. 27, 1995 now abandoned.

FIELD AND BACKGROUND OF THE INVENTION

This invention relates to the field of optical biosensors and theapplication of optical biosensors to biochemical analysis, particularlyin combination with standard biochemical analysis techniques andequipment to permit automated analysis.

Optical biosensors are devices which make use of the refractive andcoupling properties of light to detect the presence of substances on asurface. Usually integrated optical biosensors have a waveguiding film,of a certain refractive index, which forms the surface which the sampleof the substance contacts. A base sheet, which has a lower refractiveindex than the waveguiding film, contacts the waveguiding film. Agrating coupler or prism coupler is then positioned to cooperate withthe base sheet to incouple light that is shone on the base sheet throughthe coupler. Monochromatic light is then shone on the base sheet throughthe coupler and the in- or out-coupled light monitored. Changes in therefractive index of the waveguiding film caused by molecules binding toit can be detected by observing changes in the angle of the emitted,out-coupled light. To detect the presence of specific substances in thesample, the waveguiding film can be coated with a complementarysubstance which specifically binds to the first substance.

An example of a biosensor that uses a grating coupler is disclosed inEuropean Patent 0 226 604 B. This biosensor comprises a base sheetjoined to a waveguiding film; the surfaces of the sheet and film thatjoin together being formed into a grating coupler or Bragg coupler. Thisgrating coupler can be a unidiffractive or multidiffractive structure.The refractive index of the waveguiding film is higher than that of thebase sheet. A chemo-sensitive substance is coated on the waveguidingfilm in an area of the waveguiding film that contacts the sample. Alaser is used to direct monochromatic light towards the grating couplerat a selected angle of incidence. The position of the laser or of thegrating coupler is then altered to change the angle of incidence untillight is incoupled in the waveguiding film. Any change in the effectiverefractive index caused by molecules binding to the waveguiding film,disturbs the incoupling condition and the angle of incidence must bechanged to correct for this. Hence changes in the angle of incidence(and this correlates directly to the position of the laser with respectto the grating coupler) required to maintain the incoupled light aremonitored. These changes in the angle of incidence are then correlatedto changes in the amount of molecules binding to the surface of thechemo-sensitive substance.

It will be appreciated that this biosensor provides an extremelyconvenient means for detecting the presence and the amount of asubstance in a sample. However a drawback of the system is that thelaser or grating coupler must be continually moved.

A further optical biosensor is disclosed in WO 93/01487 and this opticalbiosensor permits the encoupled light to be monitored without the use ofmoving parts. This biosensor relies on the use of a fan-shaped,monochromatic light field which may be coupled in and out of thewaveguiding structure. The outcoupled light field can be focussed to apoint and the position of the point determined. Movement in the positionof the point indicates changes in the effective refractive index of thewaveguiding structure.

Optical biosensors provide a very convenient means of detecting thepresence of substances without the use expensive reagents and labellingtechniques. However at the present time, optical biosensors can only beused to test single samples which must be placed in special detectioncells. Hence the laboratory technician must transport a sample to theoptical biosenor, load it into the biosensor, and monitor it. Afterwardsthe biosensor must be cleaned. This severely limits the application ofoptical biosensors.

SUMMARY OF THE INVENTION

Accordingly in one aspect this invention provides a detection cell foruse as a component of an optical biosenor; the detection cell comprisinga transparent base plate and a sample plate on the base plate; thesample plate having a matrix of wells extending through it to eachreceive a sample, and the base plate including a waveguiding film and adiffraction grating means to incouple an incident light field into thewaveguiding film beneath a well to generate a diffracted light field toenable the detection of a change in the effective refractive index ofthe waveguiding film.

Preferably the detection cell is of the same size and contains the samenumber of wells as a microtitre plate. Usually microtitre plates contain6, 24 or 96 wells but the number of wells can vary as desired. Thereforethe detection cell provides the significant advantage that it can beused in conjunction with standard fluid-handling systems existent inanalytical laboratories. The fluid handling systems can be used to cleanthe detection cell, and pipette samples into the detection cell, andmove the detection cell from one position to the other. The opticalbiosensor, of which the detection cell is a component, can then be usedto analyse the contents of each well. Plainly the detection cell neednot have a standard number of wells, any number of wells can be used.

The base plate may be formed of a base sheet that is covered by thewaveguiding film that has a higher refractive index than the base sheet.The diffraction grating means may be formed in the base sheet, betweenthe base sheet and the waveguiding film, or in the waveguiding film.Preferably the diffraction grating means is formed in the interfacebetween the waveguiding film and the base sheet.

The base plate may be releasibly fixed to the sample plate so that itcan be detached from the sample plate and replaced.

A separate diffraction grating means may be provided beneath each wellor a single diffraction grating means, that extends over substantiallythe entire base plate, may be provided.

Preferably the waveguiding film is made of metal-oxide based materialssuch as Ta₂ O₅, TiO₂, TiO₂ --SiO₂, HfO₂, ZrO₂, Al₂ O₃, Si₃ N₄, HfON,SiON, scandium oxide or mixtures thereof. Also suitable silicon nitridesor oxynitrides (for example HfO_(x) N_(y)) may be used. However,especially suited materials are Ta₂ O₅, HfO₂, Si₃ N₄, ZrO₂, Al₂ O₃medium oxide, or a mixture of SiO₂ and TiO₂ or one of the oxinitridesHfON or SiON, especially TiO₂. Preferably the waveguiding film has arefractive index in the range 1.6 to 2.5. Also the thickness of thewaveguiding film may be varied over the range 20 to 1000 nm, preferably30 to 500 nm. The grating coupler preferably has a line density of 1000to 3000 lines per mm, for example 1200 to 2400 lines per mm.

The base sheet is preferably made of glass or plastics (polycarbonates)and preferably has a refractive index in the range 1.3 to 1.7, forexample 1.4 to 1.6.

Preferably the free surface of the waveguiding film is coated with acoupling layer that permits selective coupling of a specific substancein a well to the coupling layer. In this way, inaccuracies may bereduced. The coupling layer may be such that a reaction between it andthe specific substance occurs resulting in a covalent bond or may relyon some other form of selective coupling such as antibody/antigenbinding. Plainly the waveguiding film need not have a coupling layer ifphysical absorption, for example, of the specific substance to itprovides sufficient selectivity.

In another aspect this invention provides an analytical systemcomprising a detection cell as defined above and a reading unit thatcomprises (i) at least one light source to generate and direct at leastone incident light field onto the diffraction grating means beneath awell of the detection cell to provide mode excitation in the waveguidingfilm; (ii) at least one focusing means to focus the light fielddiffracted out of the waveguiding film beneath the well; and (iii) atleast one position sensitive detector to monitor the position of thefocussed light field.

Preferably the incident light field is generated by a laser. Alsopreferably more than one incident light field is provided; a light fieldbeing provided for each column of the matrix of the detection cell. Ifmore than one light field is provided, they may be generated byproviding (i) more than one light source, (ii) by splitting the field ofa single light source, or (iii) by expanding a light field. Similarlymore than one light detector may be provided; one light detector foreach light field.

The analytical system may also comprise a transport means to transportthe detection cell, from a filling station in which the wells of thedetection cell are filled, to a position to enable cooperation with thereading unit.

The transport means may include position locking means so that thedetection cell may be locked into exactly the same position with respectto the reading unit on each occasion that it is desired. However theoutcoupled light field alternatively may be scanned whilst the detectioncell is moving with respect to the reading unit.

In a further aspect this invention provides a method for the automatedanalysis of samples using an optical biosensor, the method comprisingfilling the wells of a detection cell as defined above with a carrierfluid; transporting the detection cell to a position to cooperate with areading unit as defined above; monitoring the out-coupled light fromeach well and recording it to provide a reference; transporting thedetection cell to a pipetting station and pipetting a sample into eachwell; transporting the detection cell back to the reading unit anddirecting light onto the diffraction grating means in the detectioncell; monitoring the out-coupled light from each well; and comparing theresults obtained to the reference.

In a yet further aspect this invention provides a method for measuringthe kinetics of a change in a sample, the method comprising filling thewells of a detection cell as defined above with a sample; transportingthe detection cell to a position to enable cooperation with the readingunit as defined above; and monitoring repeatedly at discrete intervalsthe different diffracted light fields from each well; the time of eachdiscrete interval for any cell being less than the time required for thechange.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the invention are now described, by way of example only,with reference to the drawings in which:

FIG. 1 is a perspective view of a detection plate;

FIG. 2 is a cross-section on 2--2 of FIG. 1;

FIG. 3 is an expanded view of area 3 of FIG. 2;

FIG. 4 is a schematic illustration of a biosensor system including adetection cell and a reading unit;

FIGS. 5(a) to 5(h) illustrate schematically several configurations forthe diffraction grating means beneath a well;

FIGS. 6(a) and 6(b) illustrate, schematically, configurations in whichthe absolute outcoupling angle may be determined; and

FIGS. 7(a) to 7(g) illustrate schematically several configurations forthe diffraction grating means.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Referring to FIGS. 1 and 2, the detection cell 2 is similar in shape andappearance to a standard microtitre plate (in this case, a 96 wellplate). The detection cell 2 is formed of a sample plate 4 which isrectangular in plan and which has ninety-six wells 6 extending throughit; from its upper surface to its lower surface. The wells 6 arearranged in a matrix of eight columns and twelve rows, each row beingspaced an equal distance from its neighbors and each column being spacedan equal distance from its neighbours. A base sheet 8 is affixed to thelower surface of the sample plate 4 and seals off the bottom of thewells 6. The base sheet 8 is preferably releasibly attached to thesample plate 4 so that it can be removed from the sample plate 4. Thisenables the base sheet 8 to be better washed or treated, or to bereplaced when necessary.

The base plate consisting of base sheet 8 and waveguiding film 12 canalso be irreversibly attached to the sample plate 4. This is attainedfor instance when the base plate and the sample plate 4 areultrasonically welded together. Ultrasonic welding is possible althoughthe waveguiding film 12 is not made up of a plastic material.

The base sheet 8 is made of a suitable transparent material such asglass or plastics (for example, polycarbonates), and contains adiffraction grating 10 beneath each well 6. As is best illustrated inFIG. 3, the diffraction grating 10 is formed by a serrated interfacebetween-the base sheet 8 and a waveguiding film 12. The waveguiding film12 has a refractive index of about 2.43 (which is higher than that ofthe base sheet 8) and is made of TiO₂. Other suitable materials such asTa₂ O₅, TiO₂, TiO₂ --SiO₂, HfO₂, ZrO₂, Al₂ O₃, Si₃ N₄ niobium oxide,scandium oxide, oxynitrides (for example HfO_(x) N_(y)), or mixturesthereof may be used. The thickness of the waveguiding film 12 is in theregion of 20 to 500 nm. The density of the gratings of the diffractiongrating 10 is conveniently about 1000 to 3000 lines per mm.

The diffraction grating 10 may be manufactured by lithography, embossingtechniques or injection moulding.

The bottom of each well 6 may be covered with a coupling layer 14 towhich only specific substances will selectively bind. For example, thecoupling layer 14 can be made of an antibody which has been raisedagainst a specific antigen. Therefore, if this antigen is present in thesample in the well 6, it will bind to the antibody in the couplinglayer. However other antigens and substances in the sample should notbind to the coupling layer 14. This coupling layer 14 may be precoatedon the waveguiding film 12 or may be coated on by a technician beforeuse. Also the coupling layer 14 may be permanent or removable.

Referring to FIG. 4, an example of a detection cell 2 in use is nowdescribed. First, a detection cell 2 with or without a selected couplinglayer 14 is chosen. The detection cell 2 is filled with a carrier fluidusing fluid-handling equipment conventionally used with microtitreplates and is moved for example in the direction of Arrow C over a laser16. A suitable laser is a He-Ne laser (632.8 nm) or a laser diode. Asthe detection cell 2 moves, the beam of light from the laser 16 strikesthe diffraction grating 10 of the first well 6 in a column. This beam oflight is incoupled in the waveguiding film 12 and the out-coupled beamis directed at a detector 18 where its position is detected andrecorded. A suitable detector is a CCD array or a position sensitivedetector. The laser and detector system disclosed in WO 93/01487 may beused. Fourier lenses are suitably used to focus the outcoupled to apoint on the detector 18.

The procedure of moving the detection plate 2, scanning the diffractiongrating 10 and detecting and recording the position of the out-coupledlight is carried out for each well 6 in the column. To scan all thecolumns, a reading unit (comprising a light field and a detector) may beprovided for each column. Alternatively, a reading unit may be movedalong the row in the matrix before the detector plate 2 is moved topresent the next row in the matrix. A suitable micro-processor (notshown) may be used to analyse and store the results. It is also possibleto move the reading unit instead of the detector plate 2.

Once all wells 6 have been scanned, the detector plate 2 is moved backand samples are pipetted into the wells 6 using fluid-handling equipmentconventionally used with microtitre plates. The detector cell 2 is thenmoved back to the reading unit to scan all wells 6 as described above.The reading obtained for each well 6 after addition of the sample isthen compared to that obtained before the addition of the sample. Ifsubstances in the samples have bound to the coupling layer 14 or thefree surface of the waveguiding film 12, the reading obtained wouldchange and this would indicate the presence of the substance.

In some applications, the sample in certain wells may be replaced withcarrier fluid before the detection cell 2 is moved back to the readingunit. This would ensure that the measured changes in the readings, withrespect to the reference readings, caused by changes in the refractiveindex of the coupling layer 14, are detected.

The optical biosensor may also be used to provide information concerningthe kinetics of a change in a sample; for example reaction kinetics. Inthis case the coupling layer 14 is selected such that a specificreaction product binds to it. Then the reactants are introduced into thewell and the build up of reaction product monitored. Conveniently, thismay be done in more than one well simultaneously; each well beingmonitored for a discrete time and then the next well being monitored andso on before returning to monitor the first well again. However the timetaken to cycle back to any well must be less (preferably much less) thanthe time taken for the reaction to reach completion. It is also possibleto use multiple incident-light fields to monitor several wellssimultaneously. This will remove the need to cycle between wells.

Since an optical biosensor detects small changes in angles, it isnecessary (if no other steps are taken) for the detector cell 2, afterthe wells have been filled with a sample, to be returned to exactly thesame spacial and angular position with respect to the reading unit aspreviously. If this is not done, the measurements taken cannot becompared with the reference measurements.

The need for precise positioning of the light beam with respect to thediffraction grating may be avoided (i) by the use of an extended gratingstructure which may be unidiffractional or multidiffractional (this isillustrated in FIGS. 5(a) and 5(b)) or (ii) discrete diffraction gratingstructures which are moved continuously with respect to the incidentlight beam (or vice versa). Mode excitation occurs when the incidentlight field impinges on an incoupling grating. Position sensitivedetectors 18 then measure the positions of the outcoupled light beams;preferably at the positions of maximum incoupling. In this way, the needto return the detector cells 2 to exactly the same position with respectto the light beam can be avoided.

To prevent small inaccuracies in the angular position of the detectioncell, the reading unit is preferably such that each well is illuminatedwith two incident light fields that induce mode excitation incounterpropagating directions. Also each of the two outcoupled lightfields is monitored with a separate position sensitive light detectorthat measures the angular position of the outcoupled light field. Theabsolute outcoupling angle may then be determined by comparing the tworeadings obtained from the position sensitive detectors. A suitablemethod of calculating the absolute outcoupling angle is described belowwith reference to FIG. 6.

The line densities of the incoupling grating may be chosen so that modeexcitation in forward and rearward directions can be brought about byone incident light field of fan shape. One part of the light beam causesmode excitation in the forward direction and the other part causes modeexcitation in the rearward direction. (this is illustrated in FIGS. 5(a)and (c)).

In FIGS. 5(a) and (b), a fan shaped, incident light beam (30) isincoupled in forward and rearward directions in a waveguiding film 12having a continuous grating. Outcoupled light in the forward directionis detected by a forward detector 32 and outcoupled light in therearward direction is detected by a rear detector 34. The detector cell2 need not have separate diffraction gratings 10 beneath each well 6;instead a single diffraction grating means that extends across most ofthe lower face of the sample plate 4 may be used. The line density ofthe grating plainly can be varied as desired and need not be the densitygiven above. Also the discrete diffraction grating structures maythemselves be composed of discrete gratings of preferably different linedensities (this is illustrated in FIGS. 5(c) to (h).

In FIGS. 5(c) and (d), a fan shaped, incident light beam (30) isincoupled in forward and rearward directions in a waveguiding film 12having an incoupling grating G_(i) positioned between two outcouplinggratings G_(o). Outcoupled light in the forward direction is detected bya forward detector 32 and outcoupled light in the rearward direction isdetected by a rear detector 34. The two outcoupling gratings G_(o) maybe replaced by a single large grating. In this case, two gratings wouldbe present in the incoupling region. By choosing a high line density forthe incoupling grating G_(i), free diffracted light, which would bedisturbing, may be minimized. The structure and placement of thegratings and bores thus also form optical isolating means for the matrixbores to avoid cross-talk between bores.

In FIGS. 5(e) and (f), a fan shaped, incident light beam (30) isincoupled in forward and rearward directions in a waveguiding film 12having two incoupling gratings G_(i) positioned about an outcouplinggrating G_(o). Outcoupled light in the forward direction is detected bya forward detector 32 and outcoupled light in the rearward direction isdetected by a rear detector 34. For simplicity, the forward and rearwardsituations are shown separately, but the two incoupling gratings G_(i)are preferably illuminated simultaneously by two, different fan shapedlight beams. The incoupling and outcoupling gratings may have the sameline density and may form one large discrete diffraction grating.

In FIGS. 5(g) and (h), a fan shaped, incident light beam (30) isincoupled in forward and rearward directions in a waveguiding film 12having two incoupling gratings G_(i) positioned about two outcouplinggratings G_(o). Outcoupled light in the forward direction is detected bya forward detector 32 and outcoupled light in the rearward direction isdetected by a rear detector 34. For simplicity, the forward and rearwardsituations are shown separately. For all off-line incubationapplications (with or without using microtitre plates) the determinationof an absolute sensor signal (for example an absolute outcoupling angle)is necessary. Outcoupling of a forward and rearward propagating modeusing one grating is described in SPIE, Vol 1141, 192 to 200.Outcoupling of a forward and rearward propagating mode using one gratingis also described in WO 93/01487.

A further possibility for determining absolute outcoupling anglesconsists in using two discrete outcoupling gratings or at least twodifferent regions of a single extended outcoupling grating.

An example is illustrated in FIG. 6 where two different outcouplinggratings G_(o) (or two different parts of one outcoupling grating) areused for outcoupling of the forward and rearward propagating mode.Incoupling occurs by diffraction of an incident, fan-shaped light fieldand this permits simultaneous excitation of two guided modes propagatingin forward and rearward directions. The two outcoupling gratings G_(o)operate as sensor gratings and are coated with a coupling layer 14. Asmay be seen from FIG. 6(a), the same grating regions would beillustrated by the forward propagating mode (or the rearward propagatingmode respectively) during the reference measurement and the measurementafter incubation.

The outcoupling angles are calculated from the positions X₋, X₊ of thefocussed light spots on the two position sensitive detectors 32, 34 (seeFIG. 6(a)). Small lateral displacements of the position sensitivedetectors 32, 34 in the x-direction with respect to the reading unit donot result in a change in the positions X₋, X₊ since Fourier lenses areused. However tilting of the position sensitive detectors with respectto the x-axis causes changes in the positions X₋, X₊. In theconfiguration illustrated in FIG. 6(a), the absolute outcoupling anglemay be calculated by first determining the absolute position X_(abs)which is defined as

    X.sub.abs =|X.sub.= -(X.sub.+ -X)/2|

where X₊ and X₋ are measured with respect to x=0 which is the meanposition of the two position sensitive detectors. The absoluteoutcoupling angle α_(abs) is then obtained from

    α.sub.abs =(X.sub.abs -D)/f

where D is the distance between the optical axes of the two Fourierlenses and f is their focal distance.

In FIG. 6(b) an arrangement is illustrated in which the beams are moreseparated angularly. Therefore a closer arrangement of the gratings ispossible.

The diffraction grating structure may contain gratings in twodirections; preferably normal directions. The gratings in one directionneed not be of the same line density as those in the opposite direction.Possible configurations are illustrated in FIGS. 7(a) to (g).

In FIGS. 7(a) to 7(e), the gratings beneath adjacent wells are discrete.In FIG. 7(a) the gratings beneath some of the wells extend at rightangles to those beneath their neighbours. In FIG. 7(b) the gratingsbeneath the wells at the edges extend at right angles to those beneaththe adjacent edge wells. In FIG. 7(c) the gratings beneath some of thewells extend in two, perpendicular directions. In FIG. 7(d), thegratings beneath wells at the edges in a row or column extend in two,perpendicular directions; the gratings beneath the remaining wellsextending in one direction only. In FIG. 7(e), the gratings beneath allwells in a row or column extend at right angles to those beneath wellsin adjacent rows or columns. In FIG. 7(f), the gratings beneath allwells in a row or column extend at right angles to those beneath wellsin adjacent rows or columns but the gratings are continuous over the rowor column. In FIG. 7(g), two perpendicular gratings extend continuouslybeneath all wells. Diffraction gratings orientated perpendicularly toeach other permit the determination of the angle of autocollimation inthe two normal directions and therefore the tilt of the base sheet 8.

The diffraction grating structure need not be positioned at theinterface between the base sheet 8 and the waveguiding film 12 but canbe positioned in the base sheet 8 or in the waveguiding film 12.

In another embodiment, a low index buffer layer may be positionedbetween the base sheet 8 and the waveguiding film 12 and the gratingintegrated in the base sheet 8. The grating may also be located at thesurface opposite to the waveguiding film 12.

It will also be appreciated that the detection cell 2 may contain asmany wells 6 as desired.

It will be appreciated that the invention can be used to detect thepresence of antigens or antibodies in a sample and hence replaceconventional immunoassays which require labelling of some sort. Also theinvention can be used to detect antigens to receptors and vice versa. Infurther applications, the invention can be used to quantify nucleotidemolecules in a sample and therefore the invention has application in PCRprocesses.

The invention provides the significant advantage that analysis ofsamples may be done in a highly automated, rapid fashion using, for themost part, conventional fluid handling equipment. Moreover, sinceoptical biosensors do not require the use of radio-labels or largequantities of reagents, little, if any, hazardous waste is produced.

We claim:
 1. A cell array plate comprising:a microtitre sample plate having a matrix of bores extending from a first surface of said sample plate through said sample plate and to an opposite second surface of said sample plate, the bores being arranged in rows and columns; a base plate arrangement having first and second opposite surfaces, and extending along said second opposite surface of said sample plate, said first surface of said base plate arrangement being in intimate contact with said opposite surface of said sample plate so as to seal said bores of said matrix along said opposite second surface of said sample plate, thereby closing said bores at a plurality of distinct surface areas; and a waveguiding film arrangement at said base plate arrangement and extending along said distinct surface areas, said base plate arrangement being transparent for light from said second surface of said base plate arrangement to said waveguiding film arrangement; said base plate arrangement comprising at least one diffraction grating structure area adjacent each of said plurality of distinct surface areas for coupling light impinging through said second surface of said base plate arrangement into said waveguiding film arrangement along a distinct surface area, and from said waveguiding film arrangement adjacent said distinct surface area, back through said second surface of said base plate arrangement; said base plate arrangement with said waveguiding film arrangement and said diffraction grating structure areas, substantially preventing light coupled into said waveguiding film arrangement at one of said plurality of distinct surface areas, from propagating into the waveguiding film arrangement at another one of said distinct surface areas neighboring said one of said distinct surface areas, and thereby substantially preventing cross-talk between said distinct surface areas.
 2. The plate of claim 1, wherein said waveguiding film arrangement comprises at least two distinct diffraction grating structure areas at each of said distinct surface areas.
 3. The plate of claim 1, wherein said waveguiding film arrangement comprises first diffraction gratings and second diffraction gratings, said first and second diffraction gratings being arranged in a rectangular pattern with respect to each other.
 4. The plate of claim 1, including an optical coupling layer extending along each of said distinct surface areas.
 5. The plate of claim 1, wherein said waveguiding film arrangement is made of titanium dioxide.
 6. The plate of claim 1, wherein said waveguiding film arrangement is made of a material comprising at least one of the oxides Ta₂ O₅, HfO₂, Si₃ N₄, ZrO₂, niobium oxide, Al₂ O₃ or a mixture of SiO₂ and TiO₂ or at least one of the oxinitrides HfON or SiON.
 7. The plate of claim 1, wherein said base plate arrangement is removably connected to said sample plate.
 8. The plate of claim 1, comprising at least three distinct diffraction gratings at each of said distinct surface areas.
 9. The plate of claim 1, wherein said waveguiding film arrangement comprises a continuous waveguiding film.
 10. The plate of claim 9, wherein a continuous diffraction grating structure area is provided along said base plate arrangement, forming said at least one diffraction grating structure area at each of said distinct surface areas.
 11. The plate of claim 1, wherein said base plate arrangement includes a base plate, said waveguiding film arrangement being deposited on said base plate.
 12. The plate of claim 11, wherein each diffraction grating structure area is provided at an interface between said waveguiding film arrangement and said base plate. 